Intractable diarrhea of 2 years' duration was evaluated in a patient with mixed connective tissue disease and dilatation of the proximal small bowel. Stool analysis revealed secretory diarrhea. Intestinal perfusion studies showed that the jejunum was secreting water and electrolytes. Chloride and bicarbonate secretion against an electrical gradient suggested active anion secretion. Absorption in the ileum was normal. No evidence for bacterial colonization of the small bowel, protein-losing enteropathy, or a hormonal cause of intestinal secretion could be found. This case report suggests that water and electrolyte secretion in dilated segments of small bowel may be another cause of diarrhea in cases of gastrointestinal involvement by systemic connective tissue disease.